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@#In recent years, the chimeric antigen receptor T-cell (CAR-T) therapy has achieved breakthrough progress in the treatment of hematologic malignancies. However, when it comes to solid tumors, numerous challenges persist.These include limited CAR-T cell infiltration, susceptibility to T cell exhaustion, off-target effects, and more.Thus, novel therapeutic strategies are imperative to enhance the efficacy of CAR-T therapy for solid tumors. In comparison to standalone CAR-T approaches, the combination of CAR-T with other tumor treatment modalities has demonstrated remarkable effectiveness in both preclinical and clinical research.This review article summarizes the advancements in combining CAR-T with various solid tumor treatments: antibody drugs, oncolytic viruses, tumor vaccines, and nanomedicines.The objective is to furnish a theoretical foundation and novel perspectives for the development of innovative CAR-T combination strategies tailored for solid tumor therapy.
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Regulatory T cells (Treg) are important inhibitory immune cells to establish immune tolerance, which play a pivotal role in regulating excessive immune response and autoimmune diseases of the host. Previous studies related to transplant immune tolerance have confirmed that increasing the number of Treg in vivo or enhancing the function of Treg serve as a therapeutic strategy to induce transplant immune tolerance. At present, Treg-based induction methods for transplant immune tolerance include adoptive infusion of Treg, in vivo amplification of Treg and utilization of antigen-specific Treg. In this article, the characteristics and mechanism of Treg, the latest research progress on basic experiments and clinical practice of Treg related to transplant immune tolerance at home and abroad were reviewed, and future challenges and development of Treg therapy were prospected, aiming to unravel the significance and application prospect of Treg in transplant immune tolerance, explore the advantages and limitations of Treg therapeutic strategies, and provide reference and evidence for subsequent research in this field.
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Chronic lymphocytic leukemia (CLL) is a low-grade lymphoproliferative tumor that occurs frequently in middle-aged and elderly people. Early and precise intervention can effectively improve the clinical prognosis of CLL patients. In the past, chemotherapy was the main treatment plan. With the development of molecular biology and the continuous advent of immune targeting drugs, targeted drugs targeting B cell receptor signaling pathway have shown high clinical application value in the diagnosis and treatment path of CLL. Cellular immunotherapies such as CAR-T also offer hope for patients with relapsed and refractory CLL. Allogeneic hematopoietic stem cell transplantation and multi-drug combination have also shown remarkable results in clinical practice. The purpose of this article is to review the latest research progress in the treatment of CLL.
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Humans , Hematopoietic Stem Cell Transplantation , Immunotherapy , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Signal TransductionABSTRACT
Chimeric Antigen Receptor (CAR) is a research hotspot in the field of cellular immunotherapy in recent years, and CAR-T cells therapy are developing rapidly in hematological malignant tumors, but their clinical application is still limited by related risks. It is particularly important to find more optimized immunoreactive cells. Natural killer (NK) cells, as key effector cells of innate immunity, can kill tumor or infected cells quickly without prior sensitization. Autologous or allogeneic NK cell infusion has become an effective cell therapy for acute myeloid leukemia (AML). CAR-NK cells combine the advantages of CAR targeting tumor specific antigens and enhancing immune cells activity with the innate antitumor function of NK cells to enhance the targeting and lytic activity of NK cells to AML primordial cells. At present, most of the CAR-NK treatments for AML are still in the stage of specific target screening and verification. This article reviews the latest research progress of CAR-NK cell therapy in the field of AML therapy.
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Humans , Receptors, Chimeric Antigen , Killer Cells, Natural , Leukemia, Myeloid, Acute/drug therapy , Immunotherapy, Adoptive , ImmunotherapyABSTRACT
OBJECTIVE@#To investigate the safety and efficacy of novel CD19-KIRS2/Dap12-BB chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory B-cell malignancy (R/R BCM).@*METHODS@#Three patients with R/R BCM treated with novel CD19-KIRS2/Dap12-BB CAR-T cells from June 2020 to November 2020 were enrolled, including 1 case of B-cell acute lymphoblastic leukaemia (B-ALL) and 2 cases of non-Hodgkin's lymphoma (NHL), and the efficacy and adverse reactions were observed.@*RESULTS@#After CAR-T cells infusion, patient with B-ALL achieved complete remission (CR) and minimal residual disease (MRD) turned negative, and 2 patients with NHL achieved partial remission (PR). Grade 2 cytokine release syndrome (CRS) occurred in B-ALL patient, grade 1 CRS occurred in 2 NHL patients, and grade II to IV hematologic adverse reactions occurred in 3 patients, all of which were controllable and reversible. The progression-free survival (PFS) of the 3 patients was 143, 199, and 91 days, and overall survival (OS) was 282, 430, and 338 days, respectively.@*CONCLUSION@#The novel CD19-KIRS2/Dap12-BB CAR-T cells in treatment of 3 patients with R/R BCM have significant short-term efficacy and controllable adverse reactions, but the long-term efficacy needs to be further improved.
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Humans , Receptors, Chimeric Antigen , Immunotherapy, Adoptive , Burkitt Lymphoma , Antigens, CD19 , Neoplasm, Residual , Adaptor Proteins, Signal TransducingABSTRACT
Rejection and adverse reactions caused by long-term use of immunosuppressants severely affect the survival rate and quality of life of organ transplant recipients. Immune tolerance induction plays a key role in improving the survival rate and quality of life of organ transplant recipients. In recent years, tremendous progress has been achieved in adoptive re-transfusion of regulatory cells. In this article, research progress in regulatory T cell (Treg), myeloid-derived suppressor cell (MDSC) and regulatory B cell (Breg) in animal experiment and clinical application was reviewed, and the main clinical problems of adoptive re-transfusion of regulatory cells, the application of chimeric antigen receptor Treg and the concept of cell therapy in immune evaluation were summarized, aiming to deepen the understanding of regulatory cell therapy, promote the application of regulatory cells in immune tolerance of organ transplantation, and improve clinical efficacy of organ transplantation and the quality of life of recipients.
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@#In recent years,considerable progress has been made in the treatment of multiple myeloma(MM).However,despite the current improved prognosis of this malignancy,it always ends in relapse and therefore new therapeutic approaches are urgently needed to overcome it.The chimeric antigen receptor(CAR)-T cells targeting B cell maturation antigen(BCMA),cluster of differentiation 19(CD19),cluster of differentiation 38(CD38) and kappa light chains have been evaluated,and have achieved remarkable results in clinical trials.However,even when MM is treated with CAR-T cell therapy,most patients eventually relapse,which is the greatest limitation of this therapy.This paperreviewedthe research progress,limitations and optimization of CAR-T cell immunotherapy in the treatment of MM.
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Breast cancer is the most common malignant tumor in women. It is particularly important to seek targeted therapy other than surgery, chemoradiotherapy, endocrine therapy. With the continuous exploration of tumor immunotherapy, more and more therapeutic targets have been discovered. This paper reviews therapeutic targets of chimeric antigen receptor T-cell (CAR-T) and the application in breast cancer.
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Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.
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Objective:To discuss outcomes of emergency repairing for Gustilo III B and III C fractures of forearm with complicated tissue defects and the related influence factors.Methods:From January 2014 to Feburary 2022, data of 98 cases of Gustilo III B and III C fractures with large compound defects of soft tissue, blood vessel, bone, tendon or muscle from elbow to wrist were collected. Primary debridement, bone fixation, wound coverage by free flap, bone transfer(or bone cement filling) or dynamic reconstruction of muscle were completed with emergency surgery in Department of Hand and Foot Microsurgery, Xi'an Fengcheng Hospital. Postoperative follow-ups were conducted through outpatient clinic visits, telephone and WeChat reviews. Video clips, questionnaires and the latest information of patients were also analysed. Rank sum test and Chi-square test were used to examine the relationship between independent variables such as general condition, disease condition and surgical procedures of chimeric tissue transfer group and simple flap transfer group, together with dependent variables such as limb salvage, number of surgery, wound healing, function scores, and complications. P<0.05 were further included in the regression equation to discover the relationship between multiple independent variables and dependent variables. Results:Follow-up lasted for 6-96 months, with an average of 71.1 months. In the chimeric group, the limb salvage rate was at 95.1%, with an infection rate of 8.50% and an average number of surgery was 2.13±0.89. In the simple flap transfer group, the limb salvage rate was at 87.5%, with an infection rate of 15.38% and an average number of surgery was 2.62±0.64. The good rate of Anderson score was 65.3% and the average score of Disability of the Arm, Shoulder and Hand(DASH) was 32.9(0-60) points for all the patients. There were significant differences in dependent variables of limb salvage and infection rate between the 2 groups ( P<0.05). Ischemia time and method of bone fixation led to significant differences in number of surgery ( P<0.05). Methods of bone fixation and the types of flap made significant differences in wound healing ( P<0.05). Underlying disease, bonedefect, Gustilo classification and method of bone fixation all contributed to the significant differences in function score ( P<0.05 or P<0.01) . Conclusion:Emergency surgery for repair of serious injury of forearm has a relatively high limb salvage rate and good functional effects. The limb salvage rate is not correlated with independent variables such as severity of injury, Mangledextremity Severity Score (MESS) and ischemia time, while transfer of a simple flap or a chimeric flap is significantly correlated with the limb salvage rate, infection and wound healing. The severity of injury, ischemia time and bone defect are correlated with functional assessment, number of surgery and bone healing.
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Objective:Verstaile free superficial circumflex iliac artery perforator flap(SCIAPF) were adopted for various reconstructive scenarios, and its clinical effect and value was evaluated.Methods:Retrospective analysis was performed on 42 patients with tissue defects admitted in the Department of Orthopeadic of the Second Affiliated Hospital of Wenzhou Medical University from January 2015 to May 2019. Nine patients had injury in the foot, 8 in ankle, 8 in calf, 7 in forearm, 9 in hand, and 1 in the mouth. All of the defects were repaired by SCIAPF, including 28 single soft tissue defect wounds, 8 multiple soft tissue defect, and 6 composite defects. The size of soft tissue defect were 1.2 cm×1.8 cm-14.0 cm×20.8 cm. The size of flaps were 1.5 cm×2.0 cm-15.3 cm×22.3 cm. The patients entered follow up by outpatient clinic visit and telephone reviews to observe the survival of the flaps, functional recovery and complications.Results:In this series, there were 28 flaps, including 18 pedicled with superficia branch of superficial circumflex iliac artery, 2 pedicled with deep branch of superficial circumflex iliac artery, and 8 pedicled with 2 branches. Six were chimeric flaps. Among them, 4 flaps were iliac bone flaps with superficial branch of superficial circumflex iliac artery flaps, and 2 were superficial iliac circumflex artery flap with sartorius muscle flap. Eight cases were resurfaced with lobulated SCIAPF. Arterial anastomoses: end-to-side in 35 arteries and end-to-end in 7 arteries. Venous anastomosis: end-to-end in 27 veins and end-to-side in 15 veins. Venous return through superficial iliac circumflex vein in 25 flaps, through venae comitantes in 12 flaps and through both in 5 flaps. All flap donor sites were sutured directly. All flaps survived uneventfully except for one that compromised with end-to-side anastomotic dehiscence and bleeding, and survived after re-anastomosis. All flaps and donor sites healed primarily. During the follow-up of 6-24(mean, 11.5) months, the pliable flaps were ruddy in colour and soft in texture, without obvious bloatness and pigmentation. The donor site healed well with linear scars in 35 cases and mild scar hyperplasia in 7 cases. The donor hip function were normal. Three patients suffered a numbness of the thigh caused by intraoperative injury lateral femoral cutaneous nerve and it disappeared completely after 3 months.Conclusion:New applications of lobulated or chimeric SCIAPF, based on the SCIA vasculature or its branches, can meet most of the clinical repair requirement.
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Objective:To investigate the effect of chimeric flap pedicled with superficial branch of superficial iliac circumflex artery in repair of soft tissue defect of dorsal hand combined with metacarpal bone defect.Methods:From May 2015 to January 2022, 34 patients(28 males and 6 females) of soft tissue defects of dorsal hand with metacarpal bone defects were treated in the Department of Orthopedics of Yibin Third People's Hospital. The age of patients ranged from 22 to 51 years old, with an average age of 37 years old. The areas of soft tissue defects after debridement were 2.5 cm×5.0 cm-4.5 cm×9.0 cm, and the defects were all in dorsal hand and dorsal wrist. The lengths of metacarpal bone defect were 1.8-4.1 cm. All the patients had only single metacarpal bone defect, among which: 14 patients had defects in first metacarpal bone, 7 in second metacarpal bone, 4 in third metacarpal bone, 8 in fourth metacarpal bone and 1 in fifth metacarpal bone. All the patients were repaired by chimeric flap pedicled with superficial branch of superficial iliac circumflex artery. The size of flaps were 3.6 cm×5.4 cm-5.2 cm×9.5 cm. Anticoagulation, thermal preservation and plaster fixation were applied for 4-6 weeks after surgery. Postoperative follow-ups included regularly outpatient clinic visit, telephone or Wechat reviews. Follow-up items covered: the feeling and appearance of flaps in recipient sites, healing of the donor sites and recovery of hand functions.Results:All the 34 chimeric flaps survived. Regular follow-up lasted for 3 to 15(average, 10) months. All incisions in the donor sites of hip healed in stage I. TPD of the flaps was 5.1-7.3(mean, 6.4) mm. Appearance of flaps in the receiving area were satisfactory without swelling. Movement of wrists and metacarpophalangeal joints met the basic requirement of movement. The healing time of metacarpal defect was 2-3 months with an average of 2.8 months. Hand functions were evaluated at excellent in 6 patients and good in 28, according to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association.Conclusion:The chimeric flap pedicled with superficial branch of superficial iliac circumflex artery is an ideal flap to repair the soft tissue defect in dorsal hand combined with metacarpal bone defect. It has advantages of less donor site damage, good blood supply of flap, simple surgical procedure, and one-stage repair of a combined soft tissue and metacarpal bone defects.
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Objective:To investigate the clinical and molecular characteristics of 11β-hydroxylase deficiency(11β-OHD) to improve the understanding of this disorder.Methods:The clinical manifestation, hormone level, imaging examination, characteristics of gene variation and follow-up of five patients with 11β-OHD diagnosed in Henan Children′s Hospital from 2016 to 2021 were carefully reviewed.Results:Among the 5 children, 3 were male and 2 were female, all without positive family history. The age at diagnosis was 1 year 5 months to 7 years(average 3 years and 9 months), and the bone age was 3 years 6 months to 16 years(average 10 years and 3 months). Two cases were misdiagnosed as 21-hydroxylase deficiency(21-OHD) and treated with long-term mineralocorticoids. Three patients presented with hypertension and one patient had testicular adrenal rest tumor. Adrenal CT showed bilateral adrenal hyperplasia in five patients. ACTH, 17-hydroxyprogesterone, testosterone, and androstenedione levels were increased in 5 children, and hypokalemia occurred in 1 patient. One patient carried homozygous novel missense variant, and four patients had compound heterozygous variants. Four patients carried missence mutations, two patients had deletion and one patient harbored a chimeric CYP11B2 exon1-6/CYP11B1 exon7-9. Three novel CYP11B1 mutations, including c. 1385T>C(p.L462P), c.64C>T(p.Q22*)and c. 1354G>A(p.G452R) were identified. The final height of 2 male children were 164.4 cm and 150.2 cm, respectively, and the related hormone levels of the other 3 children were normal.Conclusion:11β-OHD is easily misdiagnosed, leading to severe impairment of final height. CYP11B1 gene variation is complex and diverse, which requires variety of gene detection methods.
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Chimeric antigen receptor T (CAR-T) cell therapy is one of the most significant advances in cancer treatment in the last few decades, revolutionizing the treatment paradigm for patients with refractory / recurrent diffuse large B-cell lymphoma (R/R DLBCL) and effectively improving the survival rate of these patients. However, due to the high incidence of grade III-IV side effects of CAR-T cell therapy and the fact that some patients did not obtain remission after CAR-T cell therapy or developed rapid disease progression within a short period of time, researchers are attempting to explore combined therapies, such as chemotherapy, radiotherapy and immunotherapy, to reduce the incidence of side effects and prolong the duration of persistent remission in patients. Among these options, radiotherapy in combination with CAR-T cell therapy have been proven to improve clinical prognosis. In this article, the theoretical basis of synergistic treatment of radiotherapy and CAR-T cell therapy in patients with R/R DLBCL, the safety and efficacy of radiotherapy, the sequence of radiotherapy and CAR-T cell therapy, and the dose of the target area of radiotherapy were reviewed, aiming to provide more evidence for the application and optimization of radiotherapy combined with CAR-T cell therapy for R/R DLBCL.
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Objective:To explore the predictive value of peripheral blood cytokine models on organ functional impairment after chimeric antigen receptor T(CAR-T) cell therapy in children with B-lineage lymphocytic leukemia.Methods:The clinical data of 44 children with acute B-lineage lymphoblastic leukemia who received CAR-T cell therapy at Children′s Hospital of Soochow University from September 2018 to October 2020 were retrospectively analyzed.Peripheral blood cytokines, including interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon(IFN)-γ and IL-17A, were measured daily for 14 days after receiving CAR-T cell therapy.The trend of peripheral blood cytokine levels was analyzed at the endpoint of organ function recovery or death within 14 days after CAR-T cell treatment.Receiver operating characteristic curve was used to establish a mathematical prediction model to predict the occurrence of organ damage in the children.Results:Of the 44 children, 31 cases were boys and 13 cases were girls, with a median age of 7.96 (5.19, 11.48)years.Cytokine release syndrome(CRS) response occurred in 95.5% (42/44) children, with 88.1% (37/42) had a grade 1-3 CRS response, and 16.7% (7/42) had a severe grade 4-5 CRS response.Using IL-6>3 892.95 pg/mL as cut-off value, the area under the curve(AUC) for predicting acute respiratory failure was 0.818, with a sensitivity of 0.8 and a specificity of 0.735, while combining IFN-γ>414.4 pg/mL, IL-6>3 892.95 pg/mL and IL-2>27.05 pg/mL were the three cut-off values, with an AUC of 0.741, sensitivity of 0.6 and specificity of 0.912 for predicting acute respiratory failure. Using IFN-γ>1 699.5 pg/mL as cut-off value, the AUC for predicting shock was 0.908, with a sensitivity of 0.722 and a specificity of 1.With IL-6>4 607.3 pg/mL as cut-off value, the AUC for predicting liver injury was 0.964, with a sensitivity of 1 and a specificity of 0.906, while combining both IL-6>4 607.3 pg/mL and IFN-γ>1 446.2 pg/mL as cut-off values, the AUC for predicting liver injury was 0.977, with a sensitivity of 1 and a specificity of 0.906.Combining both IL-6>6 972.2 pg/mL and IFN-γ>3 981.5 pg/mL predicted a positive predictive value of 62.5% and a negative predictive value of 94.4% for grade 4-5 CRS response, with an AUC of 0.846, a predictive sensitivity of 0.714 and a specificity of 0.838, and all children had a combination of two or more organ function injuries.Conclusion:The combination of IL-6 and IFN-γ can effectively predict the incidence of liver injury and cytokine release syndrome.The combination of peripheral blood cytokines IFN-γ, IL-6 and IL-2 can be used to predict the incidence of acute respiratory failure after the treatment of CAR-T cells in children with acute B-lineage lymphoblastic leukaemia.IFN-γ single index can be used to predict the incidence of shock.The combination of IL-6 and IFN-γ can be used to predict the incidence of liver injury and the severity of CRS.
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Objective:To investigate the value of quantitative parameters of magnetic resonance imaging (MRI) in predicting the efficacy of chimeric antigen receptor T-cell (CAR-T) therapy for children and adolescents with mature aggressive B-cell non-Hodgkin lymphoma (NHL).Methods:It was a retrospective multicenter study.Clinical data of 44 children and adolescents diagnosed with mature aggressive B-cell NHL between January 2016 and January 2023 in Henan Cancer Hospital, Beijing Gaobo Boren Hospital, and the First Affiliated Hospital of Xinxiang Medical University were retrospectively analyzed.Patients were divided into complete response (CR) group and non-CR group based on the international criteria for the diagnosis of pediatric NHL.Quantitative parameters of MRI, including T2 signal intensity, the minimal apparent diffusion coefficient (ADCmin), maximal ADC (ADCmax), and the mean ADC (ADCmean) were measured before and within 2 weeks after CAR-T infusion.The correlation between the above parameters and the achievement of CR was analyzed.The intraclass correlation coefficient (ICC) was used to assess the inter-observer agreement among observers in measuring quantitative parameters of MRI.Differences between groups were analyzed using the independent sample t-test.Factors influencing CR were identified through the binary Logistic regression analysis, and a prediction model was established.Model performance was evaluated by plotting receiver operating characteristic (ROC) curves. Results:Significant differences were observed between the CR group and non-CR group in T2 signal intensity before CAR-T infusion (267±152 vs.364±160, P=0.048), and ADCmin (0.94±0.38 vs.0.53±0.28, P<0.05), ADCmax (1.73±0.69 vs.0.84±0.43, P<0.05), ADCmean (1.28±0.48 vs.0.67±0.33, P<0.05), and T2 signal intensity within 2 weeks after CAR-T infusion (198±139 vs.345±168, P=0.004). A univariate prediction model was created by introducing the above quantitative parameters.The area under the curve (AUC), specificity, sensitivity, and accuracy of T2 signal intensity before CAR-T infusion in predicting the efficacy on children and adolescents with mature aggressive B-cell NHL were 0.800, 84.0%, 57.9%, and 72.7%, respectively.The AUC, specificity, sensitivity, and accuracy of ADCmax within 2 weeks of CAR-T infusion were 0.958, 88.0%, 78.9%, and 84.1%, respectively.The AUC, specificity, sensitivity, and accuracy of T2 signal intensity within 2 weeks of CAR-T infusion were 0.869, 84.0%, 68.4%, and 77.3%, respectively. Conclusions:Quantitative parameters of MRI, including ADC values and T2 signal intensity, are of great significance in the early prediction of CAR-T therapy efficacy on children and adolescents with mature aggressive B-cell NHL.Among these parameters, ADCmax presents the strongest predictive performance and serves as a valuable indicator for predicting a complete response with CAR-T treatment.
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Chimeric antigen receptor T-cell (CAR-T) immunotherapy is one of the new models of tumor targeted therapy. However, the presence of cytokine release syndrome (CRS) after CAR-T infusion is a key obstacle limiting its therapeutic effects. Macrophage activation and pyrosis of target tumor cells can trigger the release of interleukin-6 and other inflammatory factors, and excessive inflammatory factors can lead to excessive activation of endothelial cells, which is a key molecular mechanism for the escalation of CRS and the occurrence of serious adverse events. Intervention in multiple stages of cytokine production and structural optimization of chimeric antigen receptor molecules are effective strategies to reduce CRS.
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Chimeric antigen receptor T cell (CAR-T) therapy, an emerging immunotherapy, has achieved remarkable results in the treatment of hematologic tumors. However, it's limited in the treatment of solid tumors such as esophageal squamous cell carcinoma due to various factors. Clarifying the reasons for the limitation of CAR-T therapy and exploring the corresponding solutions can provide new ideas and insights for the treatment of esophageal squamous cell carcinoma.
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Chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved good efficacy in treatment of hematological malignancies. As a precise and individualized treatment method, CAR-T is gradually moving towards commercialization. In addition to the introduction of corresponding policies and guiding principles, the related detection protocols should also be updated and improved to maximize its effect and achieve precise individualization. This article introduces and expands the concept of "companion diagnostics" that first appeared in targeted drugs, and introduces the significances of various detection technologies and biomarkers for patient screening, safety monitoring and evaluation of efficacy and CAR-T function in the whole process of CAR-T treatment.
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Chronic lymphocytic leukemia (CLL) is a clonal malignant disease of B lymphocytes (T lymphocytes are rare) and usually occurs in elderly people. CLL has a highly variable clinical course, with a median survival of 35 to 63 months. In the era of immunochemotherapy, the survival of CLL patients has improved significantly, but most patients still have primary drug resistance and relapse after the treatment. The emergence of Bruton tyrosine kinase inhibitor has completely changed the treatment mode of CLL, making the treatment of CLL into the era of targeted therapy. Ibrutinib combined with CD19 chimeric antigen receptor T-cell has good efficacy and can improve the prognosis of patients.